Disruption of nasopharyngeal epithelium by pneumococci is density‐linked

Lagrou, Katrien; Peetermans, Willy; Verhaegen, Jan; Jorissen, Mark; Eldere, Johan Van

doi:10.1046/j.1365-2362.2003.01144.x

Cited by 2 publications

(2 citation statements)

References 11 publications

(13 reference statements)

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“…Particular efforts have been made to characterize the interaction of H. influenzae with respiratory epithelium and to identify the compounds responsible for the decrease in CBF after exposure to a culture filtrate of H. influenzae (Ferguson et al 1988;Read et al 1992). S. pneumoniae appears to have an effect on nasopharyngeal integrity (Lagrou et al 2003) but no direct effect on CBF was observed (Ferguson et al 1988). P. aeruginosa has been shown to release factors that cause slowing of human nasal cilia in-vitro (Wilson et al 1985), and attempts have been made to identify these factors (Hingley et al 1986).…”

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confidence: 99%

Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins

Mallants

Jorissen

Augustijns

2008

Journal of Pharmacy and Pharmacology

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In the present study, we explored whether the cilio-inhibitory effect induced by toxins derived from bacterial infections could be compensated for by a cilio-stimulatory effect of antibiotics. Human nasal epithelial cells (HNEC) expressing beating cilia were grown as monolayers. Ciliary beat frequency (CBF) was determined using an inverted microscope coupled with a high-speed digital camera. Clarithromycin and neomycin did not influence ciliary activity. Bacitracin, clindamycin, gramicidin and roxithromycin increased CBF significantly: by 50 +/- 12%, 54 +/- 16%, 31 +/- 16% and 31 +/- 18%, respectively. A 30 min exposure to Staphylococcus aureus enterotoxin B (SEB) and Pseudomonas aeruginosa lipopolysaccharide (PAL) decreased CBF significantly, by 37 +/- 16 and 28 +/- 12%, respectively. In contrast with exposure to the toxin alone, co-incubation of the nasal monolayer cells with PAL and bacitracin or clindamycin did not result in a decrease in CBF after 30 and 60 min. The effect of SEB could be compensated for by bacitracin but not by clindamycin. After a 12 h preincubation period with SEB, co-incubation with either bacitracin or clindamycin resulted in the complete recovery of CBF. This study suggests that topical antibiotic treatment of nasal infections could result in a dual positive effect, namely treatment of the bacterial infection and recovery of ciliary activity.

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confidence: 99%

Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins

Mallants

Jorissen

Augustijns

2008

Journal of Pharmacy and Pharmacology

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“…The resulting model is described by a hybrid system of five ODEs (Equation 1). The nominal values of the 24 model parameters (Table 1 ) were derived by fitting the model outcome to datasets from 11 independent studies, namely three in vivo studies (Benton et al, 1997 ; Zhang et al, 2009 and our own experiment) and eight in vitro studies (Nash et al, 1987 ; Coyne et al, 2002 ; Lagrou et al, 2003 ; Attali et al, 2008 ; Chin et al, 2008 ; Komori et al, 2011 ; Hathaway et al, 2012 ; Kwok et al, 2012 ), as detailed in the Supplementary Material. Our model therefore provides a coherent mathematical framework to explain both in vivo and in vitro data.…”

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confidence: 99%

Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment

et al. 2017

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Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We further designed optimal treatment strategies, with minimal strengths and minimal durations of antibiotics, for each of the three pathogenic behaviors distinguished by our model. The proposed mathematical framework will help to design better disease management strategies and new diagnostic markers that can be used to inform the most appropriate patient-specific treatment options.

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Disruption of nasopharyngeal epithelium by pneumococci is density‐linked

Abstract: Pneumococci cause a decrease in the TEER at a density of 1 x 107 CFU mL-1. Our hypothesis is that this decrease in the TEER is the result of quorum-induced lysis of the pneumococci.

Cited by 2 publications

References 11 publications

Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins

Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins

Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment

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